This invention relates generally to an electrical transdermal drug device delivering a drug to the patient for systemic distribution by blood flow using principles of electrokinetic phenomena, such as electrophoresis and electroosmosis, and more particularly to an electrical transdermal drug applicator using a plurality of interposed and superposed signals of varying electrical potential which extend the period of therapeutic drug delivery and thereby increase usefulness of the drug applicator. Reference to or disclosure of devices for transdermal delivery of drugs by application of electrical current through the skin of a person or animal are shown in the following U.S. Patents:
______________________________________ 385,556 4,243,052 486,902 4,325,367 588,479 4,367,745 2,493,155 4,419,019 2,267,162 4,474,570 2,784,715 4,406,658 3,163,166 4,314,554 3,289,671 4,166,457 3,547,107 4,239,052 3,677,268 4,290,878 4,008,721 4,164,226 4,141,359 4,362,645 4,239,046 4,273,135 ______________________________________
The following foreign patents refer to disclosed transdermal drug delivery devices:
EPA No. 0060452 PA1 DE No. 290202183 PA1 DE No. 3225748 PA1 EPA No. 0058920 PA1 UK No. 2104388
Thus, it is evident, that transdermal delivery of drugs by application of an electrical current is not unknown. Yet, except for experimental and developmental purposes, such electrical transdermal drug applicators are not presently commercially available for use by medical professionals or by individuals.
A problem with transdermal patches, especially electronically powered patches, is that such devices exhibit a rate of drug delivery which decays with passage of time despite a steady state condition for the applied electrical current and steady state drug concentrations within the drug reservoir of the device. This phenomenon has been reported in scientific journals, for example, an article, IN VIVO TRANSDERMAL DELIVERY OF INSULIN, Chien et al, Annals of New York Academy of Sciences, pages 38-47 (1987).
Therein, changes in blood glucose level are recorded versus time after insulin is delivered transdermally to laboratory animals using an electrical current. Several parameters are varied. For example, it is reported that a pulsed DC current has a greater and more enduring effect in reducing blood glucose levels in laboratory animals than does a pure continuous DC current. The actual quantity of insulin which is delivered is not measured. Rather the effect of the drug in reducing blood glucose levels is measured. It is found that one repetition rate of DC pulses is more effective than another pulse repetition rate in reducing blood glucose levels measured both in magnitude of reduction and time duration. A square waveform provided better results than did a sinusoidal waveform or a trapezoidal waveform.
The authors of the paper analogize the skin electrically with resistances and capacitances in parallel as an equivalent circuit. They theorize that the DC current polarizes the skin, that is, charges the capacitance of the skin which, once charged, can accept no more current and accordingly limits drug delivery. Using DC pulses rather than steady state current allows time for the skin capacitance to discharge, such that on the next pulse, additional current, capacitor charging, and drug delivery can occur.
However, an anomalous situation arises when at a favorable pulse repetition rate, and with the same current delivery level as in prior tests, the duty cycle is varied. It would be expected that the greater the duty cycle, that is, the greater the current ON time versus the current OFF time ratio, the greater amount of insulin would be delivered transdermally and the measured effects on blood glucose level would be correspondingly more favorable and more enduring. Contrary to expectations, as the duty cycle increases from a one to one ratio toward an eight to one ratio, the reduction in blood glucose level becomes less, rather than more, although duration of this glucose level reduction is somewhat extended.
In summary, application of electrical current over a longer period of time, that is, delivering more electrical energy transdermally for delivering drugs, results in what appears to be continuously decreasing delivery of drug.
That publication graphically illustrates the problem with prior art transdermal drug applicators and delivery methods using electrical current to carry drugs through the skin, that is, the effectiveness of the delivered drug is insufficient in duration and therapeutic effect and the rate of drug delivery falls off as the delivering current is continuously applied over extended periods of time.
What is needed is a transdermal drug applicator which provides enhanced drug delivery to the patient with regard to quantity of systemically delivered drug and duration of drug effectiveness.